Distraction and attention-diversion approaches are widely integrated into pain management. Music-induced analgesia, the ability of music to reduce pain perception, is a clinically-relevant approach for managing pain, anxiety and psychological well-being. Research categorizes audio-analgesic interventions as homogenous, however enquiry is required to identify which musical constructs may be therapeutically effective. This study investigated the impact of harmony and rhythm on acute, post-operative pain in a sample of 98 patients scheduled for knee surgery. Four music-listening groups were compared against controls using silent relaxation. After surgery using standardized anaesthesia, participants undertook a 15-minute intervention per day of in-patient stay. Measures of pain intensity, pain interference, salivary cortisol concentration and mood were obtained. All participants showed reductions in pain from pre- to post-test, indicating silent relaxation was as effective as music-listening. Salivary cortisol concentrations showed that music with high harmonicity/rhythmicity reduced cortisol concentration to a greater extent on Day 1 than music with low harmonicity/rhythmicity. These findings validate the homogenous use of auditory distraction for audio-analgesia, and importantly emphasize the core role of compositional musical constructs in maximizing early postoperative recovery. Results support the need for additional psychobiological research examining the efficacy of audio-analgesic attention-diversion interventions used in pain management.